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Article Effectiveness of Boric Acid in Sepsis in Rats With Cecal Perforation(Springer Nature, 2025) Kurtipek, Ali Can; Dursun, Ali Dogan; Yigman, Zeynep; Ozdemir, Cagri; Kucuk, Aysegul; Gonullu, Ugur; Arslan, MustafaIntroduction and AimSepsis is a systemic inflammatory response that develops in the host against microorganisms, which results in end-organ damage. Boric acid (BA) has been shown to have immune modulatory effects in vitro and in animal studies. The aim of the study is to investigate the effects of high dose BA on lung and kidney tissues in rats with sepsis induced by the CLP method.Method28 rats were randomly divided into four groups: Group C (control group), Group BA, Group CLP (cecal ligation and puncture), and Group CLP + BA. Cecum was ligated below the ileocecal valve and punctured. BA was administered to the treatment groups at an intraperitoneal dose of 200 mg/kg, and at the end of 24 h, lung and kidney tissue samples were collected and evaluated for biochemical and histopathological parameters.ResultsHistopathologically, in kidney tissue, CLP + BA group showed significantly less peritubular capillary dilatation and brush border loss in the proximal tubule epithelium compared to the CLP group. In lung tissue, CLP + BA group had significantly less alveolar wall thickening compared to the CLP group. Biochemical analyses indicated that BA administration reduced oxidative stress in both renal and lung tissues.ConclusionWe found that intraperitoneal administration of high dose boric acid partially ameliorated the tissue damage in rats subjected to CLP induced sepsis. Further studies are needed regarding the dosage and application at different time points.Article Organ-Protective Effects of Fullerenol and Desflurane in a Rat Model of Ischemia–Reperfusion Injury(Nature Portfolio, 2025) Kip, Gulay; Koksal, Zeynep; Yigman, Zeynep; Kucuk, Aysegul; Arslan, Mustafa; Akarca Dizakar, Saadet Ozen; Sivgin, VolkanTo investigate the protective effects of fullerenol applied before ischemia induction and desflurane anesthesia applied during ischemia-reperfusion (IR) induction in the lungs and kidneys of a lower-extremity IR injury rat model. After receiving ethical approval, we randomly divided 30 rats into five groups: sham (S), IR, IR with 100 mg/kg fullerenol (IR-FUL), IR with 6.7% desflurane (IR-DES), IR with 100 mg/kg fullerenol and 6.7% desflurane (IR-FUL-DES). Fullerenol was administered 30 min before the IR procedure in the IR-FUL and IR-FUL-DES groups, and desflurane was administered during the IR procedure in the IR-DES and IR-FUL-DES groups. During the procedure, an atraumatic microvascular clamp was placed in the aorta for 120 min. The clamp was then removed to achieve reperfusion for 120 min. Finally, at the end of reperfusion, we evaluated the extracted lung and kidney tissue samples and assessed them biochemically and histopathologically. The lung damage scores of the IR-FUL, IR-DES, and IR-FUL-DES groups were significantly lower than those of the IR group (p < .0001, p = .002, and p < .0001, respectively). The renal tubule injury scores of the IR, IR-FUL, IR-DES, and IR-FUL-DES groups were significantly higher than those of the S group (p < .0001). By contrast, the renal tubule injury scores of the IR-FUL and IR-FUL-DES groups were significantly lower than those of the IR group (p < .0001 and p = .001, respectively). Moreover, kidney intercellular adhesion molecule 1 (ICAM1) expression was significantly lower in all the treatment groups, particularly the IR-FUL group, than in the IR group, and lung ICAM1 expression was significantly lower in the IR-FUL and IR-FUL-DES groups than in the other treatment groups. In the lung and kidney tissues, thiobarbituric acid reactive substance levels, catalase activity, glutathione-S-transferase activity, and arylesterase activity were relatively high in the treatment groups. The application of fullerenol before and after desflurane anesthesia during IR has protective effects on rat lungs and kidneys. In particular, histopathology confirmed that the application of fullerenol 30 min before IR induction and desflurane anesthesia during IR induction reduced oxidative stress and alleviated IR-related damage in the lungs and kidneys. These findings may have important translational relevance, suggesting potential perioperative strategies for protecting organs from ischemia-reperfusion injury in clinical settings.Article Citation - WoS: 3Citation - Scopus: 4Effects of Cerium Oxide on Kidney and Liver Tissue Damage in an Experimental Myocardial Ischemia-Reperfusion Model of Distant Organ Damage(Mdpi, 2024) Gunes, Isin; Dursun, Ali Dogan; Ozdemir, Cagri; Kucuk, Aysegul; Sezen, Saban Cem; Arslan, Mustafa; Ozer, AbdullahBackground and Objectives: Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO2) affects systemic anti-inflammatory response and inflammation. Therefore, in our study, we aimed to investigate whether CeO2 administration has a protective effect against myocardial I/R injury in the liver and kidneys. Materials and Methods: Twenty-four rats were randomly divided into four groups after obtaining approval from an ethics committee. A control (group C), cerium oxide (group CO), IR (group IR), and Cerium oxide-IR (CO-IR group) groups were formed. Intraperitoneal CeO2 was administered at a dose of 0.5 mg/kg 30 min before left thoracotomy and left main coronary (LAD) ligation, and myocardial muscle ischemia was induced for 30 min. After LAD ligation was removed, reperfusion was performed for 120 min. All rats were euthanized using ketamine, and blood was collected. Liver and kidney tissue samples were evaluated histopathologically. Serum AST (aspartate aminotransferase), ALT (alanine aminotransaminase), GGT (gamma-glutamyl transferase), glucose, TOS (Total Oxidant Status), and TAS (Total Antioxidant Status) levels were also measured. Results: Necrotic cell and mononuclear cell infiltration in the liver parenchyma of rats in the IR group was observed to be significantly increased compared to the other groups. Hepatocyte degeneration was greater in the IR group compared to groups C and CO. Vascular vacuolization and hypertrophy, tubular degeneration, and necrosis were increased in the kidney tissue of the IR group compared to the other groups. Tubular dilatation was significantly higher in the IR group than in the C and CO groups. TOS was significantly higher in all groups than in the IR group (p < 0.0001, p < 0.0001, and p = 0.006, respectively). However, TAS level was lower in the IR group than in the other groups (p = 0.002, p = 0.020, and p = 0.031, respectively). Renal and liver histopathological findings decreased significantly in the CO-IR group compared to the IR group. A decrease in the TOS level and an increase in the TAS level were found compared to the IR group. The AST, ALT, GGT, and Glucose levels are shown. Conclusions: CeO2 administered before ischemia-reperfusion reduced oxidative stress and ameliorated IR-induced damage in distant organs. We suggest that CeO2 exerts protective effects in the myocardial IR model.Article Citation - WoS: 9Citation - Scopus: 15Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats With Experimental Alzheimer's Disease(Dove Medical Press Ltd, 2023) Ozdemir, Cagri; Arslan, Mustafa; Kucuk, Aysegul; Yigman, Zeynep; Dursun, Ali DoganIntroduction: Oxidative stress has an important role in the pathophysiology of Alzheimer's disease (AD), the most common type of dementia. Boric acid (BA) contributes significantly to the protection of the brain by reducing lipid peroxidation and supporting antioxidant defense. We aimed to evaluate the therapeutic potential of BA treatment in AD rats. Materials and Methods: Four groups were formed as Control (C), Alzheimer's (A), Alzheimer's + Boric acid (ABA), Boric acid (BA). Intracerebroventricular injection of Streptozotocin (STZ) was preferred to create an AD. After 4 weeks, BA was applied 3 times every other day. The Radial Arm Maze Test (RAMT) was used to evaluate memory and learning abilities. Biochemical and histopathological evaluations were made in the hippocampus. Results: Initial RAMT inlet/outlet (I/O) numbers were similar. Two weeks after STZ injection, I/O numbers decreased in group A and ABA compared to group C and BA (p<0.05). After the second BA application, I/O numbers increased in the ABA group compared to the A group (p<0.05). In group A, PON-1, TOS and OSI levels were higher and TAS levels were lower than in groups BA and C. After BA treatment, PON-1 and OSI levels were lower in the ABA group than in the A group (p<0.05). Although there was an increase in TAS value and a decrease in TOS, this did not make a statistical difference. The thickness of the pyramidal cell in CA1 and the granular cell layers in the dentate gyrus, and the number of intact and degenerated neurons in the pyramidal cell layer were similar between the groups. Discussion: Significant improvement in learning and memory abilities after BA application is promising for AD. Conclusion: These results show that BA application positively affects learning and memory abilities, and reduces oxidative stress. More extensive studies are required to evaluate histopathological efficacy.Article Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death(MDPI, 2025) Bozok, Ummu Gulsen; Ergorun, Aydan Iremnur; Kucuk, Aysegul; Yigman, Zeynep; Dursun, Ali Dogan; Arslan, MustafaAim: This study sought to clarify the therapeutic benefits and mechanisms of action of pomegranate seed oil (PSO) in instances of ischemia–reperfusion (IR) damage in the lower extremities. Materials and Methods: The sample size was determined, then 32 rats were randomly allocated to four groups: Control (C), ischemia–reperfusion (IR), low-dose PSO (IR + LD, 0.15 mL/kg), and high-dose PSO (IR + HD, 0.30 mL/kg). The ischemia model in the IR group was established by occluding the infrarenal aorta for 120 min. Prior to reperfusion, PSO was delivered to the IR + LD and IR + HD groups at doses of 0.15 mL/kg and 0.30 mL/kg, respectively, followed by a 120 min reperfusion period. Subsequently, blood and tissue specimens were obtained. Statistical investigation was executed utilizing Statistical Package for the Social Sciences version 20.0 (SPSS, IBM Corp., Armonk, NY, USA). Results: Biochemical tests revealed significant variations in total antioxidant level (TAS), total oxidant level (TOS), and the oxidative stress index (OSI) across the groups (p < 0.0001). The IR group had elevated TOS and OSI levels, whereas PSO therapy resulted in a reduction in these values (p < 0.05). As opposed to the IR group, TASs were higher in the PSO-treated groups. Histopathological analysis demonstrated muscle fiber degeneration, interstitial edema, and the infiltration of cells associated with inflammation in the IR group, with analogous results noted in the PSO treatment groups. Immunohistochemical analysis revealed that the expressions of Tumor Necrosis Factor-alpha (TNF-α), Nuclear Factor kappa B (NF-κB), cytochrome C (CYT C), and caspase 3 (CASP3) were elevated in the IR group, while PSO treatment diminished these markers and attenuated inflammation and apoptosis (p < 0.05). The findings demonstrate that PSO has a dose-dependent impact on IR injury. Discussion: This research indicates that PSO has significant protective benefits against IR injury in the lower extremities. PSO mitigated tissue damage and maintained mitochondrial integrity by addressing oxidative stress, inflammation, and apoptotic pathways. Particularly, high-dose PSO yielded more substantial enhancements in these processes and exhibited outcomes most comparable to the control group in biochemical, histological, and immunohistochemical investigations. These findings underscore the potential of PSO as an efficacious natural treatment agent for IR injury. Nevertheless, additional research is required to articulate this definitively.Article Protective Role of Bromelain’s Antioxidant and Anti-Inflammatory Effects in Experimental Lower Limb Ischemia-Reperfusion Injury(Nature Portfolio, 2025) Sezen, Saban Cem; Demirtas, Huseyin; Yildirim, Alperen Kutay; Ozer, Abdullah; Dursun, Ali Dogan; Kucuk, Aysegul; Arslan, MustafaIschemia-reperfusion (IR) injury is a multifaceted pathological process characterized by excessive oxidative stress and inflammatory responses upon restoration of blood flow. Bromelain, a proteolytic enzyme complex derived from pineapple, exhibits robust antioxidant and anti-inflammatory activities. This study aimed to evaluate the protective effects and underlying mechanisms of bromelain on oxidative stress and inflammation in an experimental rat model of lower limb ischemia-reperfusion injury. Twenty-four male Wistar Albino rats were randomly allocated into four groups: Sham-operated control (SHAM), Bromelain-only (BR), Ischemia-Reperfusion (IR), and Ischemia-Reperfusion with Bromelain treatment (IR + BR). Bromelain (40 mg/kg) was administered intraperitoneally before ischemia induction. The IR model involved 45 min of infrarenal abdominal aorta occlusion followed by 120 min of reperfusion. Oxidative biomarkers (total antioxidant status [TAS], total oxidant status [TOS], oxidative stress index [OSI]) and histopathological parameters (muscle atrophy, degeneration, leukocyte infiltration, internalization of nuclei, fragmentation, and hyalinization) were analyzed. Significant increases in muscle degeneration, leukocyte infiltration, nuclear internalization, fragmentation, and elevated oxidative stress biomarkers (increased TOS and OSI, decreased TAS) were observed in the IR group compared to controls. Bromelain treatment (IR + BR) significantly ameliorated these effects, reducing muscle tissue damage, inflammation, and oxidative imbalance compared to the untreated IR group. Bromelain effectively mitigates lower limb ischemia-reperfusion injury by reducing oxidative stress, restoring antioxidant capacity, and suppressing inflammatory responses. These protective effects suggest that bromelain holds potential as a therapeutic agent for managing oxidative and inflammatory damages associated with IR conditions, warranting further clinical investigation.Article Citation - WoS: 13Citation - Scopus: 16Irisin Protects Against Hind Limb Ischemia Reperfusion Injury(Dove Medical Press Ltd, 2021) Kucuk, Aysegul; Polat, Yucel; Kilicarslan, Aydan; Sungu, Nuran; Kartal, Hakan; Dursun, Ali Dogan; Arslan, MustafaAim: The aim of this study was to evaluate the effects of irisin in a murine model of hind limb ischemia reperfusion (I/R). Methods: The mice were divided into four groups (n = 6 in each group): control, irisin, ischemia reperfusion (I/R), and irisin-ischemia reperfusion (I-I/R). Irisin (0.5 mu g.g(-1), intraperitoneally [i.p.]) was administered 30 min before the I/R procedure. After 2 h of ischemia and 2.5 h of reperfusion, blood and tissue samples were taken for biochemical and histopathological analysis. The results were analyzed by Kruskal-Wallis and Mann-Whitney U-tests. Results: There was a statistically significant difference in the total antioxidant status (TAS) and total oxidant status (TOS) levels in all the groups. The TAS level in the I/R group was significantly lower than that in the control, irisin, and I-I/R groups, whereas the TOS level was significantly higher in the I/R group as compared with that in the other groups. Caspase3 activity and caspase-8 activity, indicators of inflammation, were significantly higher in the I/R and I-I/R groups as compared with those in the control and irisin groups. Conclusion: Irisin may have protective effects in skeletal muscle ischemia reperfusion injury.Conference Object The Effect of Different Doses Apelin 13 on Erythrocyte Deformability in Rats(Wiley, 2019) Dursun, Ali Dogan; Ozdemir, Cagri; Comu, Faruk Metin; Kucuk, Aysegul; Arslan, Mustafa[No Abstract Available]
